Summary 1. A growing number of ecologists are turning to the enumeration of white blood cells from blood smears (leukocyte profiles) to assess stress in animals. There has been some inconsistency and controversy in the ecological literature, however, regarding their interpretation. The inconsistencies may stem partly from a lack of information regarding how stress affects leukocytes in different taxa, and partly from a failure on the part of researchers in one discipline to consult potentially informative literature from another. 2. Here, we seek to address both issues by reviewing the literature on the leukocyte response to stress, spanning the taxa of mammals (including humans), birds, amphibians, reptiles and fish. 3. We show that much of the early literature points to a close link between leukocyte profiles and glucocorticoid levels. Specifically, these hormones act to increase the number and percentage of neutrophils (heterophils in birds and reptiles), while decreasing the number and percentage of lymphocytes. This phenomenon is seen in all five vertebrate taxa in response to either natural stressors or exogenous administration of stress hormones. For the ecologist, therefore, high ratios of heterophils or neutrophils to lymphocytes (‘H : L’ or ‘N : L’ ratios) in blood samples reliably indicate high glucocorticoid levels. Furthermore, this close relationship between stress hormones and N : L or H : L ratios needs to be highlighted more prominently in haematological assessments of stress, as it aids the interpretation of results. 4. As with hormone assays, there are challenges to overcome in the use of leukocytes profiles to assess levels of stress; however, there are also advantages to this approach, and we outline each. Given the universal and consistent nature of the haematological response to stress, plus the overwhelming evidence from the veterinary, biomedical and ecological literature reviewed here, we conclude that this method can provide a reliable assessment of stress in all vertebrate taxa.

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The use of leukocyte profiles to measure stress in vertebrates: a review for ecologists

Under the heading ‘Hypertension, diabetes, and other disorders’ on page 1358, the guidelines1 lean on the taskforce report on CVD prevention2 suggesting ‘considering a lower threshold for institution of pharmacological therapy for hypertension (130/85) for patients with established coronary heart disease (which would include patients with …

/pdf/guidelines-on-the-management-of-stable-angina-pectoris-mlw2xf0l96.pdf

Guidelines on the management of stable angina pectoris: executive summary: the task force on the management of stable angina pectoris of the European society of cardiology.

Blood neutrophils provide the first line of defense against pathogens but have also been implicated in thrombotic processes. This dual function of neutrophils could reflect an evolutionarily conserved association between blood coagulation and antimicrobial defense, although the molecular determinants and in vivo significance of this association remain unclear. Here we show that major microbicidal effectors of neutrophils, the serine proteases neutrophil elastase and cathepsin G, together with externalized nucleosomes, promote coagulation and intravascular thrombus growth in vivo. The serine proteases and extracellular nucleosomes enhance tissue factor- and factor XII-dependent coagulation in a process involving local proteolysis of the coagulation suppressor tissue factor pathway inhibitor. During systemic infection, activation of coagulation fosters compartmentalization of bacteria in liver microvessels and reduces bacterial invasion into tissue. In the absence of a pathogen challenge, neutrophil-derived serine proteases and nucleosomes can contribute to large-vessel thrombosis, the main trigger of myocardial infarction and stroke. The ability of coagulation to suppress pathogen dissemination indicates that microvessel thrombosis represents a physiological tool of host defense.

Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases

The neutrophil/lymphocyte ratio (NLR) has recently been described as a predictor of mortality in patients who undergo percutaneous coronary intervention. The aim of this study was to investigate the utility of admission NLRs in predicting outcomes in patients with acute coronary syndromes (ACS). A total of 2,833 patients admitted to the University of Michigan Health System with diagnoses of ACS from December 1998 to October 2004 were followed. Patients were divided into tertiles according to NLR. The primary end point was all-cause in-hospital and 6-month mortality. The ACS cohort comprised 564 patients with ST-segment elevation myocardial infarctions and 2,269 patients with non-ST-segment elevation ACS. Patients in tertile 3 had higher in-hospital (8.5% vs 1.8%) and 6-month (11.5% vs 2.5%) mortality compared with those in tertile 1 (p <0.001). After adjusting for Global Registry of Acute Coronary Events risk profile, patients in the highest tertile were at an exaggerated risk for in-hospital (odds ratio 2.04, p = 0.013) and 6-month (odds ratio 3.88, p <0.001) mortality. Admission NLR is an independent predictor of in-hospital and 6-month mortality in patients with ACS. This relatively inexpensive marker of inflammation can aid in the risk stratification and prognosis of patients diagnosed with ACS.

Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome.

A systematic review of cohort studies, randomized trials, voluntary notifications to national regulatory authorities, and published case reports was undertaken to assess the incidence and characteristics of adverse effects in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. For statins other than cerivastatin, the incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate supported by data from 20 randomized controlled trials. Case fatality was 10%. Incidence was about 10 times greater when gemfibrozil was used in combination with statins. Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). In persons taking simvastatin, lovastatin, or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially erythromycin and azole antifungals), and 19% involved fibrates, principally gemfibrozil. The incidence of myopathy in patients treated with statins, estimated from cohort studies supported by randomized trials, was 11 per 100,000 person-years. For liver disease, randomized trials reported fewer hepatobiliary disorders in patients allocated statins than in those allocated placebo. The notification rate of liver failure to regulatory authorities was about 1 per million person-years of statin use. Randomized trials show no excess of renal disease or proteinuria in statin-allocated participants, and the decline in glomerular filtration rate was smaller with statins than with placebo. Evidence from 4 cohort studies and case reports suggests that statins cause peripheral neuropathy, but the attributable risk is small (12 per 100,000 person-years). No change in cognitive function was found in randomized trials of statins in elderly patients.

Statin Safety: A Systematic Review

Which White Blood Cell Subtypes Predict Increased Cardiovascular Risk

A recent European case-control study suggested that statins increase the risk for polyneuropathy, a rare but serious neurologic condition. This risk was assessed in 272 patients with idiopathic polyneuropathy and 1,360 matched controls in the Intermountain Health Care electronic database. It was found that statin use before diagnosis was not significantly greater in patients than controls (odds ratio 1.30, 95% confidence interval 0.3 to 2.1, p = 0.27), nor were doses different between patients and controls.

Do statins increase the risk of idiopathic polyneuropathy

Background: The potential of cardiac magnetic resonance (CMR) imaging to provide precise and reproducible measurements might not be realized currently. Methods: We acquired CMR images on 30 healthy adults and compared readings of 2 experienced physicians to determine sources of measurement variability. Results: Simultaneous review of tracings revealed 3 major sources of interobserver variability: 1) choice of end- diastolic/end-systolic frames; 2) choice of the most basal left and right ventricular short-axis slices; and, 3) approach to endocardial edge selection. Study Plan. These objectives were to be achieved through a prospective study in an adequate number of healthy subjects. Qualifying subjects were to undergo a stan- dardized functional CMR evaluation. Predefined cardiovas- cular measurements were made using workstation-specific methods. Key volume and mass measurements were to be performed independently by 2 observers to improve accu- racy, to determine reproducibility, and to develop consensus methods. Results were to be used for clinical and research

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Aaron N. Weaver

Papers

Which White Blood Cell Subtypes Predict Increased Cardiovascular Risk

Do statins increase the risk of idiopathic polyneuropathy

Normal Cardiac Magnetic Resonance Measurements and Interobserver Discrepancies in Volumes and Mass Using the Papillary Muscle Inclusion Method